The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.